Breaking Staphylococcus aureus biofilms with the antimicrobial lipopeptide humimycin and its synthetic analogs
The growing burden of biofilm-associated infections and antibiotic resistance driven by Staphylococcus aureus underscores the urgent need for new antimicrobial agents and new strategies. To address this challenge, antimicrobial lipopeptides like humimycins have emerged as promising candidates for co...
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Elsevier
2025-09-01
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| Series: | The Microbe |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950194625002778 |
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| author | Md Ramim Tanver Rahman Florence Henley Ismail Fliss Eric Biron |
| author_facet | Md Ramim Tanver Rahman Florence Henley Ismail Fliss Eric Biron |
| author_sort | Md Ramim Tanver Rahman |
| collection | DOAJ |
| description | The growing burden of biofilm-associated infections and antibiotic resistance driven by Staphylococcus aureus underscores the urgent need for new antimicrobial agents and new strategies. To address this challenge, antimicrobial lipopeptides like humimycins have emerged as promising candidates for combating Staphylococcus aureus biofilms. In this study, humimycin A 1 and five structural analogs (2-6) were synthesized via solid-phase peptide synthesis and evaluated for antimicrobial and antibiofilm activity against S. aureus ATCC 29213. Minimum inhibitory concentrations (MIC) and minimum biofilm inhibitory concentrations (MBIC) values were determined using broth microdilution and crystal violet staining assays, respectively. Scanning electron microscopy (SEM) was used to visualize changes in biofilm morphology, while sliding motility assays assessed the impact on virulence-associated bacterial movement. The newly introduced analogs displayed MIC values ranging from 2 to 16 µg/mL, with analog 6 showing the strongest activity. In biofilm inhibition assays, analogs 5 and 6 exhibited MBIC of 4 µg/mL and 2 µg/mL, respectively, up to 16-fold lower than the parental compound. Treatment of mature biofilms with analogs 3–6 at four times the MIC led to biomass reductions ranging from 74.8 % to 89.8 %. Scanning electron microscopy confirmed disrupted biofilm architecture following treatment. Furthermore, analogs 4 and 6 significantly inhibited sliding motility, a virulence factor linked to colonization. Resistance development was not observed after 10 serial passages under sub-MIC treatments. These findings highlight the therapeutic potential of synthetic humimycin analogs as precision antibiofilm agents against S. aureus infections. |
| format | Article |
| id | doaj-art-effafd274fbd4080b8f6cbb61e1b752f |
| institution | Kabale University |
| issn | 2950-1946 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | The Microbe |
| spelling | doaj-art-effafd274fbd4080b8f6cbb61e1b752f2025-08-22T04:59:06ZengElsevierThe Microbe2950-19462025-09-01810050910.1016/j.microb.2025.100509Breaking Staphylococcus aureus biofilms with the antimicrobial lipopeptide humimycin and its synthetic analogsMd Ramim Tanver Rahman0Florence Henley1Ismail Fliss2Eric Biron3Faculty of Pharmacy, Université Laval, Québec, Québec G1V 0A6, Canada; Laboratory of Medicinal Chemistry, CHU de Québec Research Center, Québec, Québec G1V 4G2, Canada; Institute of Nutrition and Functional Foods and Research Center in Infectious Diseases, Université Laval, Québec, Québec G1V 0A6, CanadaFaculty of Pharmacy, Université Laval, Québec, Québec G1V 0A6, Canada; Laboratory of Medicinal Chemistry, CHU de Québec Research Center, Québec, Québec G1V 4G2, Canada; Institute of Nutrition and Functional Foods and Research Center in Infectious Diseases, Université Laval, Québec, Québec G1V 0A6, CanadaInstitute of Nutrition and Functional Foods and Research Center in Infectious Diseases, Université Laval, Québec, Québec G1V 0A6, Canada; Department of Food Science, Faculty of Agriculture and Food Sciences, Université Laval, Québec, Québec G1V, CanadaFaculty of Pharmacy, Université Laval, Québec, Québec G1V 0A6, Canada; Laboratory of Medicinal Chemistry, CHU de Québec Research Center, Québec, Québec G1V 4G2, Canada; Institute of Nutrition and Functional Foods and Research Center in Infectious Diseases, Université Laval, Québec, Québec G1V 0A6, Canada; Corresponding author at: Faculty of Pharmacy, Université Laval, Québec, Québec G1V 0A6, Canada.The growing burden of biofilm-associated infections and antibiotic resistance driven by Staphylococcus aureus underscores the urgent need for new antimicrobial agents and new strategies. To address this challenge, antimicrobial lipopeptides like humimycins have emerged as promising candidates for combating Staphylococcus aureus biofilms. In this study, humimycin A 1 and five structural analogs (2-6) were synthesized via solid-phase peptide synthesis and evaluated for antimicrobial and antibiofilm activity against S. aureus ATCC 29213. Minimum inhibitory concentrations (MIC) and minimum biofilm inhibitory concentrations (MBIC) values were determined using broth microdilution and crystal violet staining assays, respectively. Scanning electron microscopy (SEM) was used to visualize changes in biofilm morphology, while sliding motility assays assessed the impact on virulence-associated bacterial movement. The newly introduced analogs displayed MIC values ranging from 2 to 16 µg/mL, with analog 6 showing the strongest activity. In biofilm inhibition assays, analogs 5 and 6 exhibited MBIC of 4 µg/mL and 2 µg/mL, respectively, up to 16-fold lower than the parental compound. Treatment of mature biofilms with analogs 3–6 at four times the MIC led to biomass reductions ranging from 74.8 % to 89.8 %. Scanning electron microscopy confirmed disrupted biofilm architecture following treatment. Furthermore, analogs 4 and 6 significantly inhibited sliding motility, a virulence factor linked to colonization. Resistance development was not observed after 10 serial passages under sub-MIC treatments. These findings highlight the therapeutic potential of synthetic humimycin analogs as precision antibiofilm agents against S. aureus infections.http://www.sciencedirect.com/science/article/pii/S2950194625002778Antimicrobial peptidesBiofilmLipopeptidesNon-ribosomal peptidesAntibiofilm activitySynthetic analogs |
| spellingShingle | Md Ramim Tanver Rahman Florence Henley Ismail Fliss Eric Biron Breaking Staphylococcus aureus biofilms with the antimicrobial lipopeptide humimycin and its synthetic analogs The Microbe Antimicrobial peptides Biofilm Lipopeptides Non-ribosomal peptides Antibiofilm activity Synthetic analogs |
| title | Breaking Staphylococcus aureus biofilms with the antimicrobial lipopeptide humimycin and its synthetic analogs |
| title_full | Breaking Staphylococcus aureus biofilms with the antimicrobial lipopeptide humimycin and its synthetic analogs |
| title_fullStr | Breaking Staphylococcus aureus biofilms with the antimicrobial lipopeptide humimycin and its synthetic analogs |
| title_full_unstemmed | Breaking Staphylococcus aureus biofilms with the antimicrobial lipopeptide humimycin and its synthetic analogs |
| title_short | Breaking Staphylococcus aureus biofilms with the antimicrobial lipopeptide humimycin and its synthetic analogs |
| title_sort | breaking staphylococcus aureus biofilms with the antimicrobial lipopeptide humimycin and its synthetic analogs |
| topic | Antimicrobial peptides Biofilm Lipopeptides Non-ribosomal peptides Antibiofilm activity Synthetic analogs |
| url | http://www.sciencedirect.com/science/article/pii/S2950194625002778 |
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